Why Hasn’t Knowing Your DNA Sequence Become a Routine Part of Health Care?

Interviewer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research show is on The Scope. In the near future having our genetic code sequenced will be as routine as taking a blood test. Dr. Gabor Marth has been recruited to co-lead the new Center for Genetic Discovery at the University of Utah. They are building a pipeline for quickly translating a patient's genome into meaningful health information.
Dr. Marth, how long do you think it will take until it becomes routine for a patient to have his DNA sequenced?

Dr. Gabor Marth: It's probably anywhere between two to five years depending on the hospital, depending on the healthcare system.

Interviewer: Oh that soon you think?

Dr. Gabor Marth: Technologically, it will be possible in just a couple of years I believe.

Interviewer: So the stumbling block at this point is not the sequencing itself. That technology is pretty much there. What are the hurdles that still need to be overcome?

Dr. Gabor Marth: The price of sequencing has come down significantly. Sequencing the very first human genome took in the neighborhood of a billion dollars. Today it's much, much cheaper. Maybe in the neighborhood of $10,000. It's also possible to do it for cheaper in bulk.
So it's not necessarily the price but also it's that it takes time to sequence a human genome. The analysis of the human genome is still not quite worked out so there are analytical challenges there are also challenges for interpreting the information that comes out of it. As I mentioned in some cases we actually understand, we know how to interpret it, but for many diseases we don't quite understand the link between genetics and disease.

Interviewer: It seems like if we're going to incorporate genetic information into healthcare it'll take sort of an overhaul of the healthcare system because you have to go all the way from, as you said, the analytics to getting the physicians and genetic counselors to know how to interpret that data.

Dr. Gabor Marth: Yes, so it's a very large bottleneck. In the research domain we can interpret a sequence and interpret human genome but to turn these into diagnostic knowledge and therapeutic decisions requires a whole infrastructure that's simply not there yet. The information has to be somehow entered into the electronic medical record and those avenues, the data standards, a lot of the technical underpinnings are still not there so this in fact one of the missions for The Center for Genetic Discovery that Dr. Mark Yandell and myself will be co-directing is to build that information highway that is necessary to sequence genetic DNA information all the way down to clinical use.

Interviewer: So you said there are many steps to get to those treatment choices. What is your specialty?

Dr. Gabor Marth: My specialty is actually fairly early on in the process. So my laboratory is developing algorithms, computational algorithms and software to analyze DNA sequences after the come off the machine. The specialty of my laboratory is the detection and discovery of genetic sequence variations which are the genetic changes that cause genetic disease or can contribute to susceptibility to genetic disease.

Interviewer: So is the problem that when you're looking at maybe tens of thousands or hundreds of thousands of sequences, how do you distinguish the harmless changes from ones that may have an impact on health?

Dr. Gabor Marth: That's a very, very difficult problem and this is the primary expertise of the other co-director Dr. Yandell who has developed the computational algorithms that does just this. Is able to, based on sequence information and additional information about the disease also potentially family relationships, is able to separate out and pick out the very few sequence variations that are likely to causative of the disease.

Interviewer: Part of what you work is the problem of big data. What is big data in this context and what are the problems that you're trying to overcome?

Dr. Gabor Marth: The type of big data The Center for Genetic Discovery will be mainly concerned with are mainly DNA sequence data. Each individual genome has over three billion nucleotides or bases and that data has to be stored efficiently and analyzed for us to make genetic discoveries.
Now you can imagine if you have to store thousands, tens of thousands or millions of genomes that represent a tremendous storage and data analysis problem, so one of the research areas that I'm involved in is to organize data in such a way that we are able to quickly access just those sections of the data that are relevant to a particular question and analyze these potentially in seconds.

Interviewer: And I'm sure that problem becomes more and more difficult as more and more people get their genomes sequenced. I mean, you may be talking about analyzing millions of sequences.

Dr. Gabor Marth: At some point all of humanity will be sequenced. Potentially not just one genome per individual because remember we may be talking about cancer patients. Individual tumor biopsies have different genomes that all need to analyzed so we might be talking about a large number of genomes per sample so we're talking about a lot of data that will be collected over the next few years.
The current systems are not really prepared to organize and analyze these data so although this potentially can be viewed as purely technical but being able to do that will determine our ability to actually analyze millions of genomes effectively over the next few years and that, as you asked earlier, this will be, in my opinion, one of the biggest bottlenecks for analyzing cohorts of samples.

Interviewer: There are different types of genomes that you'll be looking at. Can you explain that?

Dr. Gabor Marth: The genomes of almost every cell in a human are almost identical with slight changes that can occur in the lifespan of the individual. These are called somatic changes, for example, induced by radiation. During tumorigenesis, that is the formation of tumors, the genomes of cells can be altered very, very significantly. You can, in extreme cases, you can lose complete chromosomes, you can have multiple copies of other chromosomes, a large number of smaller scale genetic changes. Each tumor cell in effect has its own genome that's different from the tumor cell next to it. Because of this tumor sequencing is even more data intensive and more analysis intensive and this will be one of the areas where we have a lot interest moving forward.

Interviewer: And how does tumor genome analysis potentially help a patient with those tumors?

Dr. Gabor Marth: If you're able to sequence an individual's tumors you're, for example, able to classify the tumor sub-type, understand the specific mutations, the genetic mutations that are present in the tumor genome. You will be able to find the right therapy, the right drug, to treat that human's genome.

Interviewer: Now you've been involved with sequencing and analyzing the human genome since the beginning really. I mean, for the last 20 or 25 years with The Human Genome Project. Are you surprised at how far things have come?

Dr. Gabor Marth: That's a difficult question to answer. In some ways I talk to people about sequencing technologies and I look at DNA sequencing, the technologies that were available to sequence the first human genome and the technologies that are available today. We're seeing that today we're able to sequence a genome somewhere in the neighborhood of a million times faster than we were able to during The Human Genome Project and that's staggering progress.

Interviewer: Yeah.

Dr. Gabor Marth: But of course we don't sit on our laurels, we always want faster, we always better data, we always want more accurate data, we want more data and of course we want more understanding of what these sequences tell us about genetic predisposition to diseases.

Interviewer: And have you had your genome sequenced?

Dr. Gabor Marth: I have not, I have not yet. Maybe once I come here I'll get around to it. It will be interesting to see what my genome says about my health and my genetic future.

Interviewer: Interesting, informative and all in the name of better health. This is The Scope Health Sciences Radio.